How To Keep The Thymus Gland Healthy

Dr. Greg Fahy – Rejuvenating the Thymus to Prevent Age-related Diseases

The thymus gland is located at the height of the breastbone and is where the majority of T cells are produced by the immune system. 1 can retrieve of the thymus equally being like an ground forces military camp where new soldiers are trained and given their weapons to fight invading forces; in this case, the T cells are those soldiers, and the battlefield is your body.

As we age, the thymus begins to compress, and fewer numbers of T cells are created and trained to fight. This structural decay of the thymus is ane of the chief reasons why we become increasingly vulnerable to infectious diseases, such equally flu and pneumonia. The other reason is immune cells condign senescent.

There are a number of possible solutions to this problem. Firstly, technology new healthy and youthful thymic tissue might help to restore the immune organisation, and indeed a number of groups are working towards this.

Secondly, some researchers are focused on encouraging the anile thymus to regrow using various approaches, such as stem cell transplants, cellular reprogramming or chemical compounds. Dr. Greg Fahy is involved in researching this second arroyo, and we had the opportunity to speak to him about this work.

Introducing Dr. Greg Fahy

Hailing from California, Dr. Fahy holds a Bachelor of Science degree in Biology from the University of California at Irvine and a Ph.D. from the Medical College of Georgia in Augusta. Dr. Fahy used to be the Caput of the Tissue Cryopreservation Section of the Transfusion and Cryopreservation Inquiry Programme for the U.S. Naval Medical Research Institute in Bethesda, Maryland, where he adult the original concept of ice blocking agents.

Earlier his fourth dimension at 21st Century Medicine, where he currently is Vice President and Main Scientific Officer, Dr. Fahy pioneered the practical employ of cryopreservation past vitrification and invented a computer system to use this technology to organs at the American Carmine Cross.

With over xxx years of experience in cryobiology, Dr. Fahy is considered a globe expert in organ cryopreservation by vitrification[one-3]. He introduced the modern successful approach to vitrification for the cryopreservation process to cryobiology[iv-8], and also managed to prove that restoration of organ function afterward cryopreservation is possible.

Dr. Fahy is too a biogerontologist and is the originator and Editor-in-Chief of The Future of Crumbling: Pathways to Human Life Extension, a multi-authored volume about the futurity of biogerontology.

For 16 years, Dr. Fahy worked every bit a Managing director of the American Crumbling Association and for 6 years as the editor of Age News, the organization'southward newsletter. He currently serves on the editorial boards of Rejuvenation Research and the Open Geriatric Medicine Journal.

Dr. Fahy kindly agreed to tell usa about some of the exciting things he has been working on and, in particular, almost the studies he has been conducting on rejuvenating the thymus in humans.

Hi, Greg, thanks for finding the time to talk to our readers nearly your work. So from around age 20 (or younger) the thymus begins to shrink and loses the power to produce T cells, why does this happen?

Nobody knows why thymic atrophy, or involution, occurs, but it happens in all vertebrates, starting really at the age of puberty. Some have suggested that it happens to save energy, since the production of properly qualified T cells is very energy intensive and inefficient, and of course, at puberty, the body begins to devote more energy to reproduction, which might require a tradeoff against using energy for immune maintenance.

This could be adaptive since, in nature, humans would non have lived long plenty for immune system collapse to set in, even though today, the state of affairs is different. Regardless of the evolutionary reason for it, the near immediate biochemical cause of involution seems to be more often than not a drib in thymic FOXN1 expression, although some have pointed to a turn down in intra-thymic IL-7 and the negative influence of circulating sex hormones, for instance.

Can you please give our readers a few examples of which historic period-related diseases are promoted by the decline of thymus function.

The job of the immune organization is to fight communicable diseases and cancer, and a salubrious immune system also knows how to do these things without attacking self. With immunological crumbling or immunosenescence, all 3 of these functions weaken. T-cell-based immunity begins to collapse in the 60s, and this goes virtually to completion before 80. Coincident with this, we meet, for example, more than than xc% of seasonal flu deaths and most hospitalizations for the flu in the U.s.a. taking identify in people over 65 years of age, and the response to vaccination becoming poorer also.

Pneumonia, also, begins to become peculiarly deadly. In the 20th century, the mean man lifespan was greatly increased in large function by public wellness measures that radically diminished the death rate from infectious diseases like tuberculosis, polio, smallpox, diphtheria, etc., but yous might besides say that what also happened was to just postpone expiry from infectious diseases to afterwards threescore-65 years of age, which means that the same basic trouble nonetheless remains. Perhaps this trouble can, finally, be largely conquered by maintaining thymic role.

Twenty years ago, the part of the immune arrangement in controlling cancer was not fully appreciated, merely today, information technology is clear that a key job of the immune system is to attack and eliminate malignant and precancerous cells. In fact, some of the best cancer therapies ever created are cancer immunotherapies, in which the patient's own immune cells are harnessed to target and kill cancer cells. Then it is probably non a coincidence that in older people, the incidence of cancer skyrockets at the same fourth dimension T cell amnesty fails. The implication is that if thymic and immunological regeneration can exist accomplished, perhaps cancer incidence can be kept low throughout life, and on acme of this, if cancer does occur, mayhap immunotherapies for cancer volition exist more effective.

Finally, information technology is now accepted that the tertiary function of the thymus, which is to prevent the immune system from attacking its host, also declines with historic period. This allows chronic autoimmune reactions to accumulate with historic period, and presumably contributes to the age-related chronic inflammation that is observed to occur, which is sometimes called "inflammaging". This condition has many detrimental effects.

You recently ran a human clinical trial to regrow the thymus gland. Can you please tell us what is the principal goal of the project and what is the progress?

The trial was conducted nether an FDA-approved IND and with review from multiple scientific and ideals committees. Information technology consisted of a 12-month treatment grade for 9 men divided into two cohorts, with the first cohort starting in October of 2022 and the 2nd ending in April of this twelvemonth. Our goal was to get together preliminary evidence indicating that it is possible to safely regenerate the normal crumbling human thymus and restore its functions, substantially reversing the process of age-related immunological deterioration.

We chose to work with healthy men in office considering this was a small trial, which required a reasonably uniform population, and in part because more than information was available for men than for women. We chose an age range of fifty to 65 years because this range extends from several years before to a few years after the threshold historic period at which the immune system tends to plummet. Success would therefore suggest the possibility of preventing or fifty-fifty reversing the early stages of immune plummet. In future trials, we intend to enroll both women and older men.

The outcome measures included MRI evaluation of thymic density before and afterward treatment, simple and sophisticated assessment of T cell population distributions, measurements of many serum factors related to immune system function and full general health, lymphocyte telomere length distributions and telomerase activity, and biological age based on the Horvath epigenetic clock. Regarding our results, offset of all, when you lot're working with human beings, safety has to be the top priority, so I'm glad to exist able to say that nosotros met or exceeded all of our safety targets.

Regarding thymic imaging results, preliminary analyses indicate that there was a consistent and substantial increase in thymic density, which indicates replacement of thymic fat with more than h2o-rich cloth, and in previous studies on human being immunodeficiency patients, this coincided with improved thymic function. Superficial tests of allowed system aging showed improvements in 8 out of 9 men, and nosotros were able to identify a possible correctable reason for the failure of the 9th volunteer. Men of all ages were able to reply positively and to avoid side effects. Notwithstanding, the virtually definitive endpoints of our study are still being analyzed at four different locations around the world, and then we won't really know the last results of our study for probably another month or ii.

Are we going to run across a publication anytime soon?

I'm not certain virtually soon, merely certainly, as soon equally we tin can. This will exist a complicated paper with lots of authors and lots of data to present, but likewise with top-tier academic co-authors who tin assist us get through the scientific review process quickly. In any case, we certainly want to make certain that whatsoever novel results are shared with the broader medical and scientific communities.

Our readers are curious, what are other promising approaches to restore thymus function. Why did you choosehuman growth hormoneover using stem prison cell transplants like the 2022 experiment[ix] where they used TECs to regrow a mouse thymus?

Nosotros cull methods based on safety, efficacy, and speed. A simplified version of our handling has been independently proven to piece of work with safety in HIV patients, then in that location is already all-encompassing man clinical information suggesting that our approach will be effective in people. There is actually no alternative arroyo that has already been tested with success on people, and moving from mice to people is commonly costly, uncertain, and very time-consuming.

Accept the TEC experiments you mentioned, for example. But TECs from mouse embryonic day 14.5 to postpartum day one engrafted adequately into the thymus of adult mice, and TECs from later ages failed. Parabiosis likewise failed to regrow the adult thymus. Then, how would you apply this to humans? Mouse embryonic mean solar day 15 corresponds to the middle of the homo third trimester of gestation, so you're non going to go the needed cells from homo fetuses. You might endeavour to create the needed cells from scratch, merely nobody knows how to do that even so. Mayhap someday, someone volition figure this out, and maybe someday, long afterwards that, the FDA will actually approve that treatment, later all of the presently-unknown prophylactic issues have been worked out.

And the same is true of nearly of the other approaches y'all may have heard of or thought of yourself, the bodily human application is not likely anytime soon. An example of a potentially short-term alternative that ofttimes comes up is surgical or chemical castration. All the same, although gonadectomy regrows the thymus on some level, it doesn't always restore immune part.

Furthermore, testosterone reduces cardiovascular morbidity and mortality in men, ovariectomy shortens lifespan in mice, and transplantation of young ovaries to old mice increases their lifespan, so for both sexes, gonadal ablation may have lifespan-shortening effects, which would partly defeat the goal of thymic regeneration, non to mention the negative effects on quality of life! So this is an instance of treatments that might positively attune thymic activity but have side furnishings that partly or completely outweigh the benefits or that may take a long time to define. In contrast, our treatment is more often than not very well tolerated and even has some "positive side effects" that volunteers actually enjoy.

What we encounter is that nosotros're losing huge numbers of people to aging every day, so nosotros tin can't await. Nosotros demand something nosotros can use right now, well-nigh this infinitesimal. That's why we apply agents that the FDA already likes, or will hands similar. This should greatly simplify and speed the blessing process, and maximize the chances of success. We're on the job, and looking at every possible practical way forwards. Stay tuned!

Nosotros would similar to thank Dr. Fahy for taking the fourth dimension to speak to us almost his heady work, and we are very excited to hear that at that place has been positive progress. We look forwards to seeing the published results in the future.

Literature

[ane] Fahy, G. Grand., Wowk, B., Wu, J., Phan, J., Rasch, C., Chang, A., & Zendejas, E. (2004). Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology, 48(two), 157-178.

[2] Fahy, G. M., Wowk, B., & Wu, J. (2006). Cryopreservation of circuitous systems: the missing link in the regenerative medicine supply chain. Rejuvenation inquiry, 9(2), 279-291.

[3] Fahy, G. M., Wowk, B., Pagotan, R., Chang, A., Phan, J., Thomson, B., & Phan, L. (2009). Physical and biological aspects of renal vitrification. Organogenesis, 5(iii), 167-175.

[4] Fahy, Chiliad. K., & Hirsh, A. (1982). Prospects for organ preservation by vitrification. Organ Preservation, Basic and Practical Aspects, MTP Press, Lancaster, 399-404.

[5] Fahy, Chiliad. Chiliad., MacFarlane, D. R., Angell, C. A., & Meryman, H. T. (1984). Vitrification every bit an arroyo to cryopreservation. Cryobiology, 21(iv), 407-426.

[six] Rall, West. F., & Fahy, G. One thousand. (1985). Ice-costless cryopreservation of mouse embryos at− 196 C by vitrification. Nature, 313(6003), 573-575.

[seven] Fahy, G. M. (1986). Vitrification: a new approach to organ cryopreservation. Progress in clinical and biological research, 224, 305.

[8] Mullen, Due south. F., & Fahy, G. Grand. (2011). Fundamental aspects of vitrification as a method of reproductive cell, tissue, and organ cryopreservation. Principles & practise of fertility preservation. Cambridge Academy Printing, Cambridge, 145-163.

[9] Kim, M. J., Miller, C. M., Shadrach, J. L., Wagers, A. J., & Serwold, T. (2015). Young, proliferative thymic epithelial cells engraft and part in aging thymuses. The Periodical of Immunology, 194(ten), 4784-4795.